Variant 5-138145223-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_139199.2(BRD8):c.3391C>G(p.Pro1131Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,613,838 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 37 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 52 hom. )

Consequence

BRD8
NM_139199.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.88

Variant links:

Genes affected

BRD8 (HGNC:19874): (bromodomain containing 8) The protein encoded by this gene interacts with thyroid hormone receptor in a ligand-dependent manner and enhances thyroid hormone-dependent activation from thyroid response elements. This protein contains a bromodomain and is thought to be a nuclear receptor coactivator. Multiple alternatively spliced transcript variants that encode distinct isoforms have been identified. [provided by RefSeq, Jul 2014]

BRD8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005800903).

BP6

Variant 5-138145223-G-C is Benign according to our data. Variant chr5-138145223-G-C is described in ClinVar as [Benign]. Clinvar id is 783394.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1977/152154) while in subpopulation AFR AF= 0.0454 (1884/41510). AF 95% confidence interval is 0.0437. There are 37 homozygotes in gnomad4. There are 914 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD8	NM_139199.2 linkuse as main transcript	c.3391C>G	p.Pro1131Ala	missense_variant	25/27	ENST00000254900.10	NP_631938.2	Q9H0E9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRD8	ENST00000254900.10 linkuse as main transcript	c.3391C>G	p.Pro1131Ala	missense_variant	25/27	1	NM_139199.2	ENSP00000254900.5		Q9H0E9-1
BRD8	ENST00000427976.1 linkuse as main transcript	c.709C>G	p.Pro237Ala	missense_variant	5/6	3		ENSP00000392646.1		H7C026

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1975

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0455

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00341

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00333

AC:

837

AN:

251408

Hom.:

AF XY:

0.00235

AC XY:

319

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0455

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00149

AC:

2185

AN:

1461684

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

946

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.0503

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.00344

GnomAD4 genome

AF:

0.0130

AC:

1977

AN:

152154

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

914

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0454

Gnomad4 AMR

AF:

0.00341

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.000875

Hom.:

Bravo

AF:

0.0149

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0438

AC:

193

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00422

AC:

512

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0094

T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

N;D

REVEL

Benign

0.27

Sift

Benign

0.072

T;D

Sift4G

Benign

0.26

T;D

Polyphen

0.45

B;.

Vest4

0.24

MVP

0.32

MPC

0.12

ClinPred

0.078

GERP RS

4.9

Varity_R

0.13

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over